Abstract from the Forensic Isotope-Ratio Mass Spectrometry (FIRMS) Meeting (Sept. 17, 2002; Brands Hatch, Kent, UK) Stable Isotopic Characterization of Drug Substances and Drug Products

John P. Jasper1, Francois Fourel2, Andrew Eaton2, John Morrison2 and Andy Phillips2

1Molecular Isotope Technologies, LLC, 8 Old Oak Lane, Niantic, CT 06357 USA;

2 Micromass UK Limited, Floats Road, Wythenshawe, Manchester M23 9LZ UK

Counterfeiting of pharmaceuticals threatens consumer confidence and product efficacy, as well as the economic well-being of pharmaceutical companies. Recent studies of the natural stable-isotopic "fingerprints" of pharmaceuticals indicates a new and highly-specific method for product monitoring that will allow product identification and suppress counterfeiting.

Based on present and earlier analyses, we suggest that stable-isotopic analyses of drug substances and drug products can be used to identify individual batches of these pharmaceutical materials ("Isotopic Product Authenticity"). Such identification permits manufacturers to minimize counterfeiting, counter trading, vicarious liability, and theft. It is generally accepted that it would be much more costly to counterfeit the specific isotopic compositions of given batches of specific drug products or drug substances than it would be to purchase them legally.

Analytical results presented here of four over-the-counter analgesic drugs and four drug substances (or, Active Pharmaceutical Ingredients = APIs) show that individual batches of each material can be identified on the basis on their bulk isotopic "fingerprints." The ability to isotopically trace pharmaceuticals by the batch represents a significant advance in the area of pharmaceutical forensics. Stable isotopes are non-radioactive and exist naturally in pharmaceuticals – and in virtually all other materials. Nothing need be added to existing pharmaceutical lines to generate this batch-specific tracer of drug substances or drug products. The specificity of the technique is in one in the millions-to-billions scale, analogous to DNA identification.

Stable oxygen- (δ18O), carbon- (δ13C), nitrogen- (δ15N) and hydrogen (δD) isotopic compositions of four commercially-available analgesic drugs and four APIs strongly indicate that the majority of batches of these analgesic products have their own characteristic stable-isotopic fingerprints. In the analgesic sample suite, overall isotopic ranges and precisions are (i) for δ18O: 19.2‰ and 0.13‰ (ii) for δ13C: 20.0‰ and 0.1‰, and (iii) for δD: 24.3‰ and 2‰. In the suite of APIs, isotopic ranges and precisions are (i) for δ18O: 21.7‰ and 0.1‰ (ii) for δ13C: 21.3‰ and 0.1‰, (iii) for δ15N and 4.7 and 0.1, and (iii) for δD: 49.2‰ and 2‰.